Peptoids with Substituents on the Backbone Carbons as Conformationally Constrained Synthetic Oligoamides

Abstract

Oligo(N substituted glycine) (oligo NSG), also known as peptoid, is a synthetic oligomer with high proteolytic stability and membrane permeability due to the N substituted structures. These bene cial pharmacokinetic properties make the oligomer attractive for biological applications. However, its conformational exibility limits its utilization as protein ligands. Recently, the introduction of backbone substituents to oligo NSG has been demonstrated to restrict its own backbone bond rotations via steric interactions, and the resulting oligo(N substituted alanine) (oligo NSA) has been demonstrated to be a conformationally constrained oligomer. Here, we review the concept, history, synthetic methodologies, conformational analysis, and biological applications of the new synthetic oligomer. We also conducted overview research on N substituted peptides consisting of non α amino acid residues to facilitate the plausible future expansion of the conformationally constrained peptoids of diverse three dimensional structures.

Bottom-up design of peptide nanoshapes in water using oligomers of N-methyl-L/D-alanine

“…The conformation of the NMA residue in its oligomers is rigidified by pseudo-1,3-allylic strain, and the oligomer forms a stable extended shape [16][17][18] . These amino acid residues have hence served as attractive building blocks for the bottom-up design of peptide nanoshapes 19,20 . The bottom-up approach enables the direct design of peptide nanoshapes with a minimal number of amino acid residues.…”